摘要：SummaryTumors with an impaired transporter associated with antigen processing (TAP) present several endoplasmic reticulum-derived self-antigens on HLA class I (HLA-I) which are absent on healthy cells. Selection of such TAP-independent antigens for T cell-based immunotherapy should include analysis of their expression on healthy cells to prevent therapy-induced adverse toxicities. However, it is unknown how the absence of clinically relevant antigens on healthy cells needs to be validated. Here, we monitored TAP-independent antigen presentation on various healthy cells after establishing a T cell tool recognizing a TAP-independent signal sequence receptor 1-derived antigen. We found that most but not all healthy cells present this antigen under normal and inflammatory conditions, indicating that TAP-independent antigen presentation is a variable phenomenon. Our data emphasize the necessity of extensive testing of a wide variety of healthy cell types to define clinically relevant TAP-independent antigens that can be safely targeted by immunotherapy.Graphical AbstractDisplay OmittedHighlights•The ER-resident SSR1 holds an antigenic peptide that is processed independently of TAP•TAP-independent peptide presentation is functional in healthy cell types•TAP-independent SSR1-derived antigen presentation varies between healthy cells•This exposes safety and efficacy risks of clinical TAP-independent peptide targetingImmunology; Cancer
